Photochemistry in the dark governs pathways for singlet oxygen generation

Excited species such as singlet molecular oxygen [O2(1Δg)] and triplet carbonyls are a less understood subgroup of oxygen-derived oxidants in BioMedicine. Their generation has been associated to the detection of ultraweak chemiluminescence in mammalian tissues and there is emerging evidence for their roles in pathophysiological situations. However, pathways accounting for their generation in vivo have remained obscure, limiting the assessment of their biological roles. In vitro, excited species arise from photochemical processes involving direct excitation by light. However, atypical photochemical processes not involving photoexcitation have been proposed a number of years ago in pioneer work led, in particular, by Prof. Giuseppe Cilento, from the Chemistry Institute, University of São Paulo. Such “photochemistry in the dark” include reactions associated with dismutation of alkoxyl or alkylperoxyl radicals, pathways linked to dioxetane/oxetane decay and, particularly, triplet carbonyls arising during lipid peroxidation. Importantly, triplet carbonyls can arise from enzymatic peroxidation, raising the possibility of regulated generation of excited species in vivo. Recent work from the CEPID-Redoxoma group led by DiMascio and collaborators provided a significant step ahead to clarify this question. For that, they used chemiluminescescence, spin-trapping and mass spectrometry techniques with chemical trapping of 18O-labelled singlet molecular oxygen. The results of these studies provided unequivocal evidence that singlet molecular oxygen is generated by energy transfer from chemically as well as enzymatically-produced triplet acetone to ground state triplet molecular oxygen in aqueous phase. Thus, enzyme-catalyzed triplet carbonyls may be a source of singlet molecular oxygen even in the absence of photoexcitation. These reactions may be especially relevant in lipid environments such as membranes, given that molecular oxygen is 10 times more soluble in membranes than aqueous solution. Moreover, triplet carbonyls are well-known products of polyunsaturated fatty acid oxidation. Together, this provides a novel plausible biological route for implicating singlet molecular oxygen generation and reactivity in membrane damage and potentially in other lipid-associated diseases such as atherosclerosis and neurodegeneration.